Bone biopsy

Radiographic studies show calcium-phosphate deposits in joints and/or cardiovascular system Bone biopsy of the iliac crest... 

Lisignoli G, Toneguzzi S, Grassi F, et al. Different chemokines are expressed in human arthritic bone biopsies IFN-gamma and IL-6 differently modulate IL-8, MCP-1 and rantes production by arthritic osteoblasts. Cytokine 2002 20(5) 231-238. 

Batuman V, Wedeen RP, Bogden JD, et al. 1989. Reducing bone lead content by chelation treatment in chronic lead poisoning An in vivo X-ray fluorescence and bone biopsy study. Environ Res 48 70-75. 

The effects of raloxifene on bone histomorphometry were analyzed by Ott et al. (2002). In a group of 54 women enrolled in the MORE study, two transiliac bone biopsies were obtained at baseline and after 2 years of treatment. The results confirmed the safety of the drug on bone tissue since no woven bone, mineralization defect, cell toxicity, or medullary fibrosis was observed. Moreover, the number of empty osteocytic lacunae also suggested an antiapoptotic effect on the osteocyte. More recent experimental data further confirm this antiapoptotic effect of raloxifene on osteoblastic and osteocytic cells (Taranta et al. 2002). 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

Figure 14. An example demonstrating the boundary detection technique. A bone biopsy microradiograph from a cross section of the rib of a dog is shown in (A). The objective is to find the boundaries of the cortical bone (c), trabecular bone (T) and holes (arrows) in the cortical bone. Histogram technique is used in the spatial domain for boundary detection. The histogram is smoothed in the frequency domain. See text for description. M, marrow.

Huang, H.K., Meyers, G.L., Martin, R.K., Albright, J.P. (1983). Digital processing of microradiog-raphic and fluorochromic images from bone biopsy. Comp. Biol. Med. 13,27-47. 

Vitamin status can be assessed by a direct test for the levels of 25-(OHin the serum, This competitive binding test involves three components (1) a serum sample, (2) radioactive 25-hydroxy[ Hjvitamin Dj, and (3) vitamin D-binding protein. The source of vitamin D-binding protein may be sheep serum. The functional tests for deternrination of vitamin D irvdude the diagnostic tests for rickets and osteomalacia. A test for osteomalacia, for example, may include measurement of the width of the osteoid in a bone biopsy. The osteoid is described later. 

Vitamin D deficiency in adults cannot affect the epiphyseal plate, as it has disappeaced, but it can prevent normal mineralization of the osteoid layer in bone that turns over. In vitamin D deficiency the osteoclasts continue to create tunnels and pits in the bone. The osteoblasts continue to synthesize the protein matrix however, complete mineralization of the osteoid may not occur. The result is osteomalacia - This disease may present as bone pain about the hips. Osteomalacia can be diagnosed using a bone biopsy, A sample is taken from the iliac crest — the hip bone. An abnormally wide osteoid is indicative of the disease. X-rays can also be used to diagnose osteomalacia, which is characterized by arrays or zones of tiny fractures in sucli bones as the pelvis and femur. 

A 39-year-old woman who took high doses of aluminium and magnesium hydroxide for peptic ulcer disease (over 18 kg of elemental aluminium and 15 kg of elemental magnesium over 8 years) developed severe osteomalacia due to profound phosphate depletion (60). Bone biopsy showed stainable aluminium deposits along 28% of the total bone surface, a unique observation in a patient with normal renal function. Treatment included withdrawal of the antacid and supplementation with phosphate, calcium, and vitamin D. Her bone mineral density increased over the next 2 years. 

Immunoreactive parathyroid hormone concentrations may be increased by anticonvulsants, while bone mineral content is reduced. Hypocalcemia and osteopenia can occur, despite normal serum concentrations of active vitamin D metabolites, suggesting that they may be independent of drug effects on vitamin D metabolism. Bone biopsies have shown increased osteoid but normal calcification front formation, accelerated rate of mineralization, and reduced mineralization lag time, suggesting increased skeletal turnover rather than osteomalacia (96). The risk of age-related fractures in drug-treated epileptic patients is not greatly increased (97). 

In another child, who had osteoporotic vertebral collapse, extensive investigations showed reduced bone mineral content, reduced concentrations of osteocalcin, and features of osteoporosis on bone biopsy (SEDA-19, 344). The role of G-CSF was unclear, because bone mineral loss is a possible complication of the underlying disease. Indeed, improvement or stabilization during G-CSF treatment was noted in several patients (6). Furthermore, there was no apparent effect on height, head circumference, or weight in patients under 18 years of age (6). In another study, there was bone mineral loss with features of osteopenia/osteoporosis in 15 of 30 patients treated with G-CSF for a mean of 5.8 years for severe chronic neutropenia (65). However, six of nine patients investigated before G-CSF treatment had evidence of osteopenia/osteoporosis. 

Available bone biopsy data in dialysis patients treated for up to 4 years with lanthanum carbonate indicate low-level bone deposition, the highest concentration ever measured in any patient being 9.4 pg/ g (0.067 pmol/L). Unlike aluminium, no direct effects of lanthanum on bone have been reported so far in any clinical or experimental setting [37-39]. Ultrastructural localization demonstrated a heterogeneous distribution of lanthanum in the bone of rats and man, which was independent of the underlying type of renal osteodystrophy [40]. 

Figure 49-16 Intact PTH in assessing parathyroid function in end-stage renal disease. Dialysis patients were separated into those with early and advanced osteitis fibrosa, osteomalacia, and aplastic disease by quantitative histomorphometric analysis of undecalcified bone biopsies. (From Segre GV, Sherrard DJ, Pandian /WR, et al. Intact PTH (IRMA) II New applications to issues in parathyroid hormone and mineral metabolism. San Juan Capistrano, Calif Nichols Institute, 1989.)...

Coincident with this new technique for procurement of human bone biopsies was the development of quantitive methods of bone analysis.12 These methods include histochemical analysis of both decalcified and unde-calcified42 48 bone sections, microradiography,44 tetracycline labeling45 and autoradiography.42 The latter two techniques require administration of a tetracycline antibiotic or isotopic tracer prior to procurement of the biopsy. Undecalcified thin sections, prepared with the use of a Jung microtome after the bone core is fixed, dehydrated and embedded in methacrylate,45 are analyzed by intersect and point count methods46 47 which permit three-dimensional assessment.48 49 Tetracycline antibiotics deposit in vivo in sites of bone formation constituting markers which can be studied in undecalcified sections by fluorescence microscopy.45 47 This represents the safest and best tissue time marker for microscopic measurement of bone formation dynamics. 

The remodeling process, involving continuous resorption of both the mineralized portion of bone and the organic matrix, is coupled with the formation process and must precede it. In other words, in normal bone, formation cannot occur until resorption has taken place. In recent years much has been learned about this microscopic remodeling system which operates continuously in the entire skeleton.12 Bone cells known as osteoclasts are responsible for the resorption process. Formation and mineralization are initiated by cells known as osteoblasts. Modern histomorpho-metric techniques applied to the cells and surfaces of serial bone biopsies enable researchers to detect and quantitate malfunctions underlying the pathology in various types of metabolic bone disease. With this capability the utility of these techniques in diagnosis and evaluation of treatment are obvious. 

A multiphcity of metabolic disorders in patients with CKD contributes to worsening sHPT and the consequences associated with elevated PTH (Fig. 44-4). The continuous production of PTH by the parathyroid glands leads to parathyroid hyperplasia (nodular or diffuse). Nodular tissue demonstrates more rapid growth potential and appears to be associated with fewer vitamin D and calcium-sensing receptors, which results in resistance to the effects of calcium and vitamin D therapy and subsequent development of ROD. Bone loss can be detected in patients with early stages of kidney disease and multiple types of bone lesions have been identified from bone biopsies of patients on dialysis. The skeletal complications associated with ROD... 

Various etiologies produce differing biochemical pictures. " Determination of serum content of calcium (albumin corrected), phosphorus, alkaline phosphatase, urea nitrogen, creatinine, PTH, 25(OH) vitamin D, and calcitriol, as well as urinary calcium, creatinine, and phosphorus, can help in determining the cause, deciding on treatment, and monitoring efficacy of therapy. Definitive diagnosis is by bone biopsy. 

Khatri G, Wagner DK, Sohnle PG. Effect of bone biopsy in guiding antimicrobial therapy for osteomyelitis complicating open wounds. Am J Med Sci 2001 321 367-371. 

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